Selective organ hypothermia method and apparatus

- Innercool Therapies, Inc.

A method and apparatus for performing hypothermia of a selected organ without significant effect on surrounding organs or other tissues. A flexible catheter is inserted through the vascular system of a patient to place the distal tip of the catheter in an artery feeding the selected organ. A compressed refrigerant is pumped through the catheter to an expansion element near the distal tip of the catheter, where the refrigerant vaporizes and expands to cool a flexible heat transfer element in the distal tip of the catheter. The heat transfer element cools the blood flowing through the artery, to cool the selected organ, distal to the tip of the catheter.

Skip to: Description  ·  Claims  ·  References Cited  · Patent History  ·  Patent History
Description
CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. Ser. No. 09/306,866, filed May 7, 1999, now U.S. Pat. No. 6,235,048 and titled “Selective Organ Hypothermia Method and Apparatus”, which is a divisional application of U.S. Ser. No. 09/012,287, filed Jan. 23, 1998, titled “Selective Organ Hypothermia Method and Apparatus”, now U.S. Pat. No. 6,051,019.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable

BACKGROUND OF THE INVENTION

1. Field of the Invention

The current invention relates to selective cooling, or hypothermia, of an organ, such as the brain, by cooling the blood flowing into the organ. This cooling can protect the tissue from injury caused by anoxia or trauma.

2. Background Information

Organs of the human body, such as the brain, kidney, and heart, are maintained at a constant temperature of approximately 37° C. Cooling of organs below 35° C. is known to provide cellular protection from anoxic damage caused by a disruption of blood supply, or by trauma. Cooling can also reduce swelling associated with these injuries.

Hypothermia is currently utilized in medicine and is sometimes performed to protect the brain from injury. Cooling of the brain is generally accomplished through whole body cooling to create a condition of total body hypothermia in the range of 20° to 30° C. This cooling is accomplished by immersing the patient in ice, by using cooling blankets, or by cooling the blood flowing externally through a cardiopulmonary bypass machine. U.S. Pat. No. 3,425,419 to Dato and U.S. Pat. No. 5,486,208 to Ginsburg disclose catheters for cooling the blood to create total body hypothermia However, they rely on circulating a cold fluid to produce cooling. This is unsuitable for selective organ hypothermia, because cooling of the entire catheter by the cold fluid on its way to the organ would ultimately result in non-selective, or total body, cooling.

Total body hypothermia to provide organ protection has a number of drawbacks. First, it creates cardiovascular problems, such as cardiac arrhythmias, reduced cardiac output, and increased systemic vascular resistance. These side effects can result in organ damage. These side effects are believed to be caused reflexively in response to the reduction in core body temperature. Second, total body hypothermia is difficult to administer. Immersing a patient in ice water clearly has its associated problems. Placement on cardiopulmonary bypass requires surgical intervention and specialists to operate the machine, and it is associated with a number of complications including bleeding and volume overload. Third, the time required to reduce the body temperature and the organ temperature is prolonged. Minimizing the time between injury and the onset of cooling has been shown to produce better clinical outcomes.

Some physicians have immersed the patient's head in ice to provide brain cooling. There are also cooling helmets, or head gear, to perform the same. This approach suffers from the problems of slow cool down and poor temperature control due to the temperature gradient that must be established externally to internally. It has also been shown that complications associated with total body cooling, such as arrhythmia and decreased cardiac output, can also be caused by cooling of the face and head only.

Selective organ hypothermia has been studied by Schwartz, et. al. Utilizing baboons, blood was circulated and cooled externally from the body via the femoral artery and returned to the body through the carotid artery. This study showed that the brain could be selectively cooled to temperatures of 20° C. without reducing the temperature of the entire body. Subsequently, cardiovascular complications associated total body hypothermia did not occur. However, external circulation of the blood for cooling is not a practical approach for the treatment of humans. The risks of infection, bleeding, and fluid imbalance are great. Also, at least two arterial vessels must be punctured and cannulated. Further, percutaneous cannulation of the carotid artery is very difficult and potentially fatal, due to the associated arterial wall trauma. Also, this method could not be used to cool organs such as the kidneys, where the renal arteries cannot be directly cannulated percutaneously.

Selective organ hypothermia has also been attempted by perfusing the organ with a cold solution, such as saline or perflourocarbons. This is commonly done to protect the heart during heart surgery and is referred to as cardioplegia. This procedure has a number of drawbacks, including limited time of administration due to excessive volume accumulation, cost and inconvenience of maintaining the perfusate, and lack of effectiveness due to temperature dilution from the blood. Temperature dilution by the blood is a particular problem in high blood flow organs. such as the brain. For cardioplegia, the blood flow to the heart is minimized, and therefore this effect is minimized.

Intravascular, selective organ hypothermia, created by cooling the blood flowing into the organ, is the ideal method. First, because only the target organ is cooled, complications associated with total body hypothermia are avoided. Second, because the blood is cooled intravascularly, or in situ, problems associated with external circulation of blood are eliminated. Third, only a single puncture and arterial vessel cannulation is required, and it can be performed at an easily accessible artery such as the femoral, subclavian, or brachial. Fourth, cold perfusate solutions are not required, thus eliminating problems with excessive fluid accumulation. This also eliminates the time, cost, and handling issues associated with providing and maintaining cold perfusate solution. Fifth, rapid cooling can be achieved. Sixth, precise temperature control is possible.

Previous inventors have disclosed the circulation of a cold fluid to produce total body hypothermia, by placing a probe into a major vessel of the body. This approach is entirely unfeasible when considering selective organ hypothermia, as will be demonstrated below.

The important factor related to catheter development for selective organ hypothermia is the small size of the typical feeding artery, and the need to prevent a significant reduction in blood flow when the catheter is placed in the artery. A significant reduction in blood flow would result in ischemic organ damage. While the diameter of the major vessels of the body, such as the vena cava and aorta, are as large as 15 to 20 mm., the diameter of the feeding artery of an organ is typically only 4.0 to 8.0 mm. Thus, a catheter residing in one of these arteries cannot be much larger than 2.0 to 3.0 mm. in outside diameter. It is not practical to construct a selective organ hypothermia catheter of this small size using the circulation of cold water or other fluid. Using the brain as an example, this point will be illustrated.

The brain typically has a blood flow rate of approximately 500 to 750 cc/min. Two carotid arteries feed this blood supply to the brain. The internal carotid is a small diameter artery that branches off of the common carotid near the angle of the jaw. To cool the brain, it is important to place some of the cooling portion of the catheter into the internal carotid artery, so as to minimize cooling of the face via the external carotid, since face cooling can result in complications, as discussed above. It would be desirable to cool the blood in this artery down to 32° C., to achieve the desired cooling of the brain. To cool the blood in this artery by a 5 C.° drop, from 37° C. down to 32° C., requires between 100 and 150 watts of refrigeration power.

In order to reach the internal carotid artery from a femoral insertion point, an overall catheter length of approximately 100 cm. would be required. To avoid undue blockage of the blood flow, the outside diameter of the catheter can not exceed approximately 2 mm. Assuming a coaxial construction, this limitation in diameter would dictate an internal supply tube of about 0.70 mm. diameter, with return flow being between the internal tube and the external tube.

A catheter based on the circulation of water or saline operates on the principle of transferring heat from the blood to raise the temperature of the water. Rather than absorbing heat by boiling at a constant temperature like a freon, water must warm up to absorb heat and produce cooling. Water flowing at the rate of 5.0 grams/sec, at an initial temperature of 0° C. and warming up to 5° C., can absorb 100 watts of heat. Thus, the outer surface of the heat transfer element could only be maintained at 5° C., instead of 0° C. This will require the heat transfer element to have a surface area of approximately 1225 mm2. If a catheter of approximately 2.0 mm. diameter is assumed, the length of the heat transfer element would have to be approximately 20 cm.

In actuality, because of the overall length of the catheter, the water would undoubtedly warm up before it reached the heat transfer element, and provision of 0° C. water at the heat transfer element would be impossible. Circulating a cold liquid would cause cooling along the catheter body and could result in non-specific or total body hypothermia. Furthermore, to achieve this heat transfer rate, 5 grams/sec of water flow are required. To circulate water through a 100 cm. long, 0.70 mm. diameter supply tube at this rate produces a pressure drop of more than 3000 psi. This pressure exceeds the safety levels of many flexible medical grade plastic catheters. Further, it is doubtful whether a water pump that can generate these pressures and flow rates can be placed in an operating room.

BRIEF SUMMARY OF THE INVENTION

The selective organ cooling achieved by the present invention is accomplished by placing a cooling catheter into the feeding artery of the organ. The cooling catheter is based on the vaporization and expansion of a compressed and condensed refrigerant, such as freon. In the catheter, a shaft or body section would carry the liquid refrigerant to a distal heat transfer element where vaporization, expansion, and cooling would occur. Cooling of the catheter tip to temperatures above minus 2° C. results in cooling of the blood flowing into the organ located distally of the catheter tip, and subsequent cooling of the target organ. For example, the catheter could be placed into the internal carotid artery, to cool the brain. The size and location of this artery places significant demands on the size and flexibility of the catheter. Specifically, the outside diameter of the catheter must be minimized, so that the catheter can fit into the artery without compromising blood flow. An appropriate catheter for this application would have a flexible body of 70 to 100 cm. in length and 2.0 to 3.0 mm. in outside diameter.

It is important for the catheter to be flexible in order to ;successfully navigate the arterial path, and this is especially true of the distal end of the catheter. So, the distal end of the catheter must have a flexible heat transfer element, which is composed of a material which conducts heat better than the remainder of the catheter. The catheter body material could be nylon or PBAX, and the heat transfer element could be made from nitinol, which would have approximately 70 to 100 times the thermal conductivity of the catheter body material, and which is also superelastic. Nitinol could also be treated to undergo a transition to another shape, such as a coil, once it is placed in the proper artery. Certain tip shapes could improve heat transfer as well as allow the long tip to reside in arteries of shorter length.

The heat transfer element would require sufficient surface area to absorb 100 to 150 watts of heat. This could be accomplished with a 2 mm. diameter heat transfer tube, 15 to 18 cm. in length, with a surface temperature of 0° C. Fins can be added to increase the surface area, or to maintain the desired surface area while shortening the length.

The cooling would be provided by the vaporization and expansion of a liquid refrigerant, such as a freon, across an expansion element, such as a capillary tube. For example, freon R12 boiling at 1 atmosphere and a flow rate of between 0.11 and 0.18 liter/sec could provide between approximately 100 and 150 watts of refrigeration power. Utilizing a liquid refrigerant allows the cooling to be focused at the heat transfer element, thereby eliminating cooling along the catheter body. Utilizing boiling heat transfer to the expanded fluid also lowers the fluid flow rate requirement to remove the necessary amount of heat from the blood. This is important because the required small diameter of the catheter would have higher pressure drops at higher flow rates.

The catheter would be built in a coaxial construction with a 0.70 mm. inner supply tube diameter and a 2.0 mm. outer return tube diameter. This limits the pressure drops of the freon along the catheter length, as well as minimizing the catheter size to facilitate carotid placement. The inner tube would carry the liquid freon to the tubular heat transfer element at the distal end of the catheter body. If a heat transfer element surface temperature of 0° C. is maintained, just above the freezing point of blood, then 940 mm2 of surface area in contact with the blood are required to lower the temperature of the blood by the specified 5 C.° drop. This translates to a 2.0 mm. diameter heat transfer tube by 15 cm. in length. To generate 0° C. on the nitinol surface, the freon must boil at a temperature of minus 28° C. It is important to have boiling heat transfer, which has a higher heat transfer coefficient, to maintain the surface temperature at 0° C. There are several freons that can be controlled to boil at minus 28° C., such as a 50/50 mixture of pentafluoroethane and 1,1,1 trifluoroethane or a 50/50 mixture of difluoromethane and pentafluoroethane. The 50/50 mixture of pentafluoroethane and 1,1,1 trifluoroethane would require a flow rate of approximately 7.0 liters/min or 0.52 gram/sec to absorb 100 watts of heat. At this flow rate, the pressure drop along the inner tube is less than 7 psi in 100 cm. of length, and the pressure drop along the outer tube is less than 21 psi in 100 cm. of length.

The inner supply tube of the catheter would be connected to a condenser, fed by the high pressure side of a compressor, and the outer return tube of the catheter would be connected to the low pressure side of the compressor.

The novel features of this invention, as well as the invention itself, will be best understood from the attached drawings, taken along with the following description, in which similar reference characters refer to similar parts, and in which:

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

FIG. 1 is a schematic, partially in section, showing a first embodiment of the flexible catheter according to the present invention;

FIG. 2 is a perspective view of a second embodiment of the distal tip of the catheter of the present invention, after transformation;

FIG. 3 is a section view of a third embodiment of the distal tip of the catheter of the present invention, after expansion of the heat transfer element;

FIG. 4 is a partial section view of a fourth embodiment of the distal tip of the catheter of the present invention, after transformation;

FIG. 5 is an elevation view of a fifth embodiment of the distal tip of the catheter of the present invention, before transformation;

FIG. 6 is an elevation view of the embodiment shown in FIG. 5, after transformation to a double helix;

FIG. 7 is an elevation view of the embodiment shown in FIG. 5, after transformation to a looped coil;

FIG. 8 is an elevation view of a sixth embodiment of the distal tip of the catheter of the present invention, showing longitudinal fins on the heat transfer element;

FIG. 9 is an end view of the embodiment shown in FIG. 8;

FIG. 10 is an elevation view of a seventh embodiment of the distal tip of the catheter of the present invention, showing annular fins on the heat transfer element; and

FIG. 11 is an end view of the embodiment shown in FIG. 10.

DETAILED DESCRIPTION OF THE INVENTION

As shown in FIG. 1, the apparatus of the present invention includes a flexible catheter assembly 10, fed by a refrigeration compressor unit 12, which can include a condenser. The compressor unit 12 has an outlet 14 and an inlet 16. The catheter assembly 10 has an outer flexible catheter body 18, which can be made of braided PBAX or other suitable catheter material. The catheter body 18 must be flexible, to enable passage through the vascular system of the patient to the feeding artery of the selected organ. The inner lumen 19 of the catheter body 18 serves as the return flow path for the expanded refrigerant. The catheter assembly 10 also has an inner flexible refrigerant supply conduit 20, which can be made of nylon, polyimide, nitinol, or other suitable catheter material. The length and diameter of the catheter body 18 and refrigerant supply conduit 20 are designed for the size and location of the artery in which the apparatus will be used. For use in the internal carotid artery to achieve hypothermia of the brain, the catheter body 18 and refrigerant supply conduit 20 will have a length of approximately 70 to 100 centimeters. The catheter body 18 for this application will have an outside diameter of approximately 2.5 millimeters and an inside diameter of approximately 2.0 millimeters, and the refrigerant supply conduit will have an outside diameter of approximately 1.0 millimeter and an inside diameter of approximately 0.75 millimeter. A supply conduit 20 of this diameter will have a refrigerant pressure drop of only approximately 0.042 atmospheres per 100 centimeters. The return flow path through a catheter body 18 of this diameter will have a refrigerant pressure drop of only approximately 0.064 atmospheres per 100 centimeters.

The compressor outlet 14 is attached in fluid flow communication, by known means, to a proximal end of the refrigerant supply conduit 20 disposed coaxially within said catheter body 18. The distal end of the refrigerant supply conduit 20 is attached to an expansion element, which in this embodiment is a capillary tube 22 having a length of approximately 15 to 25 centimeters. The capillary tube 22 can be made of polyimide or nitinol, or other suitable material, and it can be a separate element attached to the supply conduit 20, or it can be an integral portion of the supply conduit 20. For the internal carotid artery application, the capillary tube 22 will have an outside diameter of approximately 0.6 millimeter and an inside diameter of approximately 0.25 millimeter. The expansion element, such as the capillary tube 22, has an outlet within a chamber of a flexible heat transfer element such as the hollow flexible tube 24. The tube 24 shown in this embodiment is flexible but essentially straight in its unflexed state. The heat transfer element must be flexible, to enable passage through the vascular system of the patient to the feeding artery of the selected organ. For the internal carotid application the flexible tube 24 will have a length of approximately 15 centimeters, an outside diameter of approximately 1.9 millimeters and an inside diameter of approximately 1.5 millimeters. The heat transfer element also includes a plug 26 in the distal end of the flexible tube 24. The plug 26 can be epoxy potting material, plastic, or a metal such as stainless steel or gold. A tapered transition of epoxy potting material can be provided between the catheter body 18 and the flexible tube 24.

A refrigerant, such as freon, is compressed, condensed, and pumped through the refrigerant supply conduit 20 to the expansion element, or capillary tube, 22. The refrigerant vaporizes and expands into the interior chamber of the heat transfer element, such as the flexible tube 24, thereby cooling the heat transfer element 24. Blood in the feeding artery flows around the heat transfer element 24, thereby being cooled. The blood then continues to flow distally into the selected organ, thereby cooling the organ.

A second embodiment of the heat transfer element is shown in FIG. 2. This embodiment can be constructed of a tubular material such as nitinol, which has a temperature dependent shape memory. The heat transfer element 28 can be originally shaped like the flexible tube 24 shown in FIG. 1, at room temperature, but trained to take on the coiled tubular shape shown in FIG. 2 at a lower temperature. This allows easier insertion of the catheter assembly 10 through the vascular system of the patient, with the essentially straight but flexible tubular shape, similar to the flexible tube 24. Then, when the heat transfer element is at the desired location in the feeding artery, such as the internal carotid artery, refrigerant flow is commenced. As the expanding refrigerant, such as a 50/50 mixture of pentafluoroethane and 1,1,1 trifluoroethane or a 50/50 mixture of difluoromethane and pentafluoroethane, cools the heat transfer element down, the heat transfer element takes on the shape of the heat transfer coil 28 shown in FIG. 2. This enhances the heat transfer capacity, while limiting the length of the heat transfer element.

A third embodiment of the expansion element and the heat transfer element is shown in FIG. 3. This embodiment of the expansion element is an orifice 30, shown at the distal end of the refrigerant supply conduit 20. The outlet of the orifice 30 discharges into an expansion chamber 32. In this embodiment, the heat transfer element is a plurality of hollow tubes 34 leading from the expansion chamber 32 to the refrigerant return lumen 19 of the catheter body 18. This embodiment of the heat transfer element 34 can be constructed of a tubular material such as nitinol, which has a temperature dependent shape memory, or some other tubular material having a permanent bias toward a curved shape. The heat transfer element tubes 34 can be essentially straight, originally, at room temperature, but trained to take on the outwardly flexed “basket” shape shown in FIG. 3 at a lower temperature. This allows easier insertion of the catheter assembly 10 through the vascular system of the patient, with the essentially straight but flexible tubes. Then, when the heat transfer element 34 is at the desired location in the feeding artery, such as the internal carotid artery, refrigerant flow is commenced. As the expanding refrigerant cools the heat transfer element 34 down, the heat transfer element takes on the basket shape shown in FIG. 3. This enhances the heat transfer capacity, while limiting the length of the heat transfer element.

A fourth embodiment of the heat transfer element is shown in FIG. 4. This embodiment can be constructed of a material such as nitinol. The heat transfer element 36 can be originally shaped as a long loop extending from the distal end of the catheter body 18, at room temperature, but trained to take on the coiled tubular shape shown in FIG. 4 at a lower temperature, with the heat transfer element 36 coiled around the capillary tube 22. This allows easier insertion of the catheter assembly 10 through the vascular system of the patient, with the essentially straight but flexible tubular loop shape. Then, when the heat transfer element 36 is at the desired location in the feeding artery, such as the internal carotid artery, refrigerant flow is commenced. As the expanding refrigerant cools the heat transfer element down, the heat transfer element takes on the shape of the coil 36 shown in FIG. 4. This enhances the heat transfer capacity, while limiting the length of the heat transfer element 36. FIG. 4 further illustrates that a thermocouple 38 can be incorporated into the catheter body 18 for temperature sensing purposes.

Yet a fifth embodiment of the heat transfer element is shown in FIGS. 5, 6, and 7. In this embodiment, an expansion element, such as a capillary tube or orifice, is incorporated within the distal end of the catheter body 18. This embodiment of the heat transfer element can be constructed of a material such as nitinol. The heat transfer element is originally shaped as a long loop 40 extending from the distal end of the catheter body 18, at room temperature. The long loop 40 has two sides 42, 44, which are substantially straight but flexible at room temperature. The sides 42, 44 of the long loop 40 can be trained to take on the double helical shape shown in FIG. 6 at a lower temperature, with the two sides 42, 44 of the heat transfer element 40 coiled around each other. Alternatively, the sides 42, 44 of the long loop 40 can be trained to take on the looped coil shape shown in FIG. 7 at a lower temperature, with each of the two sides 42, 44 of the heat transfer element 40 coiled independently. Either of these shapes allows easy insertion of the catheter assembly 10 through the vascular system of the patient, with the essentially straight but flexible tubular loop shape. Then, when the heat transfer element 40 is at the desired location in the feeding artery, such as the internal carotid artery, refrigerant flow is commenced. As the expanding refrigerant cools the heat transfer element down, the heat transfer element 40 takes on the double helical shape shown in FIG. 6 or the looped coil shape shown in FIG. 7. Both of these configurations enhance the heat transfer capacity, while limiting the length of the heat transfer element 40.

As shown in FIGS. 8 through 11, the heat transfer element 24 can have external fins 46, 48 attached thereto, such as by welding or brazing, to promote heat transfer. Use of such fins allows the use of a shorter heat transfer element without reducing the heat transfer surface area, or increases the heat transfer surface area for a given length. In FIGS. 8 and 9, a plurality of longitudinal fins 46 are attached to the heat transfer element 24. The heat transfer element 24 in such an embodiment can have a diameter of approximately 1.0 millimeter, while each of the fins 46 can have a width of approximately 0.5 millimeter and a thickness of approximately 0.12 millimeter. This will give the heat transfer element an overall diameter of approximately 2.0 millimeters, still allowing the catheter to be inserted into the internal carotid artery.

In FIGS. 10 and 11, a plurality of annular fins 48 are attached to the heat transfer element 24. The heat transfer element 24 in such an embodiment can have a diameter of approximately 1.0 millimeter, while each of the fins 48. can have a width of approximately 0.5 millimeter and a thickness of approximately 0.12 millimeter. This will give the heat transfer element an overall diameter of approximately 2.0 millimeters, still allowing the catheter to be inserted into the internal carotid artery.

While the particular invention as herein shown and disclosed in detail is fully capable of obtaining the objects and providing the advantages hereinbefore stated, it is to be understood that this disclosure is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended other than as described in the appended claims.

Claims

1. An apparatus for causing hypothermia in at least a portion of a mammal, said apparatus comprising:

a source of working fluid;
a flexible elongated catheter, said catheter having a flexible tubular outer catheter body;
a flexible tubular inner working fluid supply conduit located within said outer catheter body, a proximal end of said inner working fluid supply conduit being connected in fluid flow communication with an outlet of said source of working fluid;
a working fluid return path within said outer catheter body, a proximal end of said working fluid return path being connected in fluid flow communication with an inlet of said source of working fluid;
a flexible elongated, hollow, heat transfer element mounted to said distal end of said outer catheter body, said heat transfer element having an enhanced heat transfer surface area; and
a chamber defined within said hollow heat transfer element, said chamber being connected in fluid flow communication with an outlet of said working fluid supply conduit, said chamber being connected in fluid flow communication with a distal end of said working fluid return path within said outer catheter body;
wherein:
said working fluid supply conduit is substantially coaxial with said catheter body; and
said working fluid return path surrounds said working fluid supply conduit.

2. An apparatus for causing hypothermia in at least a portion of a mammal, said apparatus comprising:

a source of working fluid;
a flexible elongated catheter, said catheter having a flexible tubular outer catheter body;
a flexible tubular inner working fluid supply conduit located within said outer catheter body, a proximal end of said inner working fluid supply conduit being connected in fluid flow communication with an outlet of said source of working fluid;
a working fluid return path within said outer catheter body, a proximal end of said working fluid return path being connected in fluid flow communication with an inlet of said source of working fluid;
a flexible elongated, hollow, heat transfer element mounted to said distal end of said outer catheter body, said heat transfer element having an enhanced heat transfer surface area; and
a chamber defined within said hollow heat transfer element, said chamber being connected in fluid flow communication with an outlet of said working fluid supply conduit, said chamber being connected in fluid flow communication with a distal end of said working fluid return path within said outer catheter body;
wherein said heat transfer element comprises a plurality of elongated elements; and
wherein said plurality of elongated elements comprise a plurality of hollow tubes leading from said working fluid supply conduit to said working fluid return path in said catheter body, said hollow tubes being outwardly expandable.

3. An apparatus for causing hypothermia in at least a portion of a mammal, said apparatus comprising:

a source of working fluid;
a flexible elongated catheter, said catheter having a flexible tubular outer catheter body;
a flexible tubular inner working fluid supply conduit located within said outer catheter body, a proximal end of said inner working fluid supply conduit being connected in fluid flow communication with an outlet of said source of working fluid;
a working fluid return path within said outer catheter body, a proximal end of said working fluid return path being connected in fluid flow communication with an inlet of said source of working fluid;
a flexible elongated, hollow, heat transfer element mounted to said distal end of said outer catheter body, said heat transfer element having an enhanced heat transfer surface area; and
a chamber defined within said hollow heat transfer element, said chamber being connected in fluid flow communication with an outlet of said working fluid supply conduit, said chamber being connected in fluid flow communication with a distal end of said working fluid return path within said outer catheter body;
wherein said heat transfer element comprises a hollow tube coiled around said working fluid supply conduit.

4. An apparatus for causing hypothermia in at least a portion of a mammal, said apparatus comprising:

a source of working fluid;
a flexible elongated catheter, said catheter having a flexible tubular outer catheter body;
a flexible tubular inner working fluid supply conduit located within said outer catheter body, a proximal end of said inner working fluid supply conduit being connected in fluid flow communication with an outlet of said source of working fluid;
a working fluid return path within said outer catheter body, a proximal end of said working fluid return path being connected in fluid flow communication with an inlet of said source of working fluid;
a flexible elongated, hollow, heat transfer element mounted to said distal end of said outer catheter body, said heat transfer element having an enhanced heat transfer surface area; and
a chamber defined within said hollow heat transfer element, said chamber being connected in fluid flow communication with an outlet of said working fluid supply conduit, said chamber being connected in fluid flow communication with a distal end of said working fluid return path within said outer catheter body;
wherein said heat transfer element comprises a double helix.

5. An apparatus for causing hypothermia in at least a portion of a mammal, said apparatus comprising:

a source of working fluid;
a flexible elongated catheter, said catheter having a flexible tubular outer catheter body;
a flexible tubular inner working fluid supply conduit located within said outer catheter body, a proximal end of said inner working fluid supply conduit being connected in fluid flow communication with an outlet of said source of working fluid;
a working fluid return path within said outer catheter body, a proximal end of said working fluid return path being connected in fluid flow communication with an inlet of said source of working fluid;
a flexible elongated, hollow, heat transfer element mounted to said distal end of said outer catheter body, said heat transfer element having an enhanced heat transfer surface area; and
a chamber defined within said hollow heat transfer element, said chamber being connected in fluid flow communication with an outlet of said working fluid supply conduit, said chamber being connected in fluid flow communication with a distal end of said working fluid return path within said outer catheter body;
wherein said heat transfer element comprises a hollow tube in the form of a loop having two sides, each side of said loop comprising a coil.

6. An apparatus for causing hypothermia through intravascular cooling, said apparatus comprising:

a compressor;
a flexible elongated catheter, said catheter having a flexible tubular catheter body;
a flexible tubular refrigerant supply conduit within said catheter body, a proximal end of said refrigerant supply conduit being connected in fluid flow communication with an outlet of said compressor;
a refrigerant return path within said catheter body, a proximal end of said refrigerant return path being connected in fluid flow communication with an inlet of said compressor;
an expansion element adjacent to a distal end of said catheter body, said expansion element having an inlet at a distal end of said refrigerant supply conduit;
a flexible heat transfer element mounted to said distal end of said catheter body; and
a refrigerant chamber within said heat transfer element, said refrigerant chamber being connected in fluid flow communication with an outlet of said expansion element, said refrigerant chamber being connected in fluid flow communication with a distal end of said refrigerant return path within said catheter body;
wherein said heat transfer element comprises a hollow coiled tube.

7. A method for causing hypothermia through intravascular cooling, said method comprising:

providing a flexible catheter, said catheter having a heat transfer element adjacent its distal tip, said heat transfer element having an enhanced heat transfer surface area;
inserting said catheter through the vascular system of a patient to place said heat transfer element in a blood vessel;
supplying a working fluid to said heat transfer element;
passing said working fluid through said heat transfer element to cool the interior of said hollow heat transfer element;
cooling blood flowing in said vessel with said heat transfer element; and
forming said heat transfer element as a hollow coiled tube.

8. A method for causing hypothermia through intravascular cooling, said method comprising:

providing a flexible catheter, said catheter having a heat transfer element adjacent its distal tip, said heat transfer element having an enhanced heat transfer surface area;
inserting said catheter through the vascular system of a patient to place said heat transfer element in a blood vessel;
supplying a working fluid to said heat transfer element;
passing said working fluid through said heat transfer element to cool the interior of said hollow heat transfer element;
cooling blood flowing in said vessel with said heat transfer element; and
forming said heat transfer element as a hollow tube coiled around said working fluid supply conduit.

9. A method for causing hypothermia through intravascular cooling, said method comprising:

providing a flexible catheter, said catheter having a heat transfer element adjacent its distal tip, said heat transfer element having an enhanced heat transfer surface area;
inserting said catheter through the vascular system of a patient to place said heat transfer element in a blood vessel;
supplying a working fluid to said heat transfer element;
passing said working fluid through said heat transfer element to cool the interior of said hollow heat transfer element;
cooling blood flowing in said vessel with said heat transfer element; and
forming said heat transfer element as multiple helices.

10. A method as recited in claim 9, further comprising forming said multiple helices as a double helix.

11. A method as recited in claim 10, further comprising forming said double helix with each said helix being disposed to coil around said working fluid supply conduit.

12. A method as recited in claim 9, further comprising forming said multiple helices with each said helix being disposed to coil around said working fluid supply conduit.

13. A method as recited in claim 12, further comprising forming said multiple helices as a triple helix.

14. A method for causing hypothermia through intravascular cooling, said method comprising:

providing a flexible catheter, said catheter having a heat transfer element adjacent its distal tip, said heat transfer element having an enhanced heat transfer surface area;
inserting said catheter through the vascular system of a patient to place said heat transfer element in a blood vessel;
supplying a working fluid to said heat transfer element;
passing said working fluid through said heat transfer element to cool the interior of said hollow heat transfer element;
cooling blood flowing in said vessel with said heat transfer element; and
forming said heat transfer element as a hollow tube in the form of a loop having two coiled sides.

15. A method for causing hypothermia through intravascular cooling, said method comprising:

providing a flexible catheter, said catheter having a heat transfer element adjacent its distal tip, said heat transfer element having an enhanced heat transfer surface area;
inserting said catheter through the vascular system of a patient to place said heat transfer element in a blood vessel;
supplying a working fluid to said heat transfer element;
passing said working fluid through said heat transfer element to cool the interior of said hollow heat transfer element; and
cooling blood flowing in said vessel with said heat transfer element;
wherein said heat transfer element comprises a plurality of hollow tubes leading from said working fluid supply conduit to a working fluid return path in said catheter, said method further comprising expanding said plurality of hollow tubes outwardly.

16. An apparatus for causing hypothermia in at least a portion of a mammal, said apparatus comprising:

a source of working fluid;
a flexible elongated catheter, said catheter having a flexible tubular outer catheter body;
a flexible elongated, hollow, heat transfer element mounted to said distal end of said outer catheter body, said heat transfer element having an enhanced heat transfer surface area;
a flexible tubular inner working fluid supply conduit located within said outer catheter body, from an outlet of said source of working fluid to said heat transfer element; and
a working fluid return path within said outer catheter body, from said heat transfer element to an inlet of said source of working fluid;
wherein:
said working fluid supply conduit is substantially coaxial with said catheter body; and
said working fluid return path surrounds said working fluid supply conduit.

17. An apparatus for causing hypothermia in at least a portion of a mammal, said apparatus comprising:

a source of working fluid;
a flexible elongated catheter, said catheter having a flexible tubular outer catheter body;
a flexible elongated, hollow, heat transfer element mounted to said distal end of said outer catheter body, said heat transfer element having an enhanced heat transfer surface area;
a flexible tubular inner working fluid supply conduit located within said outer catheter body, from an outlet of said source of working fluid to said heat transfer element; and
a working fluid return path within said outer catheter body, from said heat transfer element to an inlet of said source of working fluid;
wherein said heat transfer element comprises a plurality of elongated elements; and
wherein said plurality of elongated elements comprise a plurality of hollow tubes leading from said working fluid supply conduit to said working fluid return path in said catheter body, said hollow tubes being outwardly expandable.

18. An apparatus for causing hypothermia in at least a portion of a mammal, said apparatus comprising:

a source of working fluid;
a flexible elongated catheter, said catheter having a flexible tubular outer catheter body;
a flexible elongated, hollow, heat transfer element mounted to said distal end of said outer catheter body, said heat transfer element having an enhanced heat transfer surface area;
a flexible tubular inner working fluid supply conduit located within said outer catheter body, from an outlet of said source of working fluid to said heat transfer element; and
a working fluid return path within said outer catheter body, from said heat transfer element to an inlet of said source of working fluid;
wherein said heat transfer element comprises a hollow tube coiled around said working fluid supply conduit.

19. An apparatus for causing hypothermia in at least a portion of a mammal, said apparatus comprising:

a source of working fluid;
a flexible elongated catheter, said catheter having a flexible tubular outer catheter body;
a flexible elongated, hollow, heat transfer element mounted to said distal end of said outer catheter body, said heat transfer element having an enhanced heat transfer surface area;
a flexible tubular inner working fluid supply conduit located within said outer catheter body, from an outlet of said source of working fluid to said heat transfer element; and
a working fluid return path within said outer catheter body, from said heat transfer element to an inlet of said source of working fluid;
wherein said heat transfer element comprises a double helix.

20. An apparatus for causing hypothermia in at least a portion of a mammal, said apparatus comprising:

a source of working fluid;
a flexible elongated catheter, said catheter having a flexible tubular outer catheter body;
a flexible elongated, hollow, heat transfer element mounted to said distal end of said outer catheter body, said heat transfer element having an enhanced heat transfer surface area;
a flexible tubular inner working fluid supply conduit located within said outer catheter body, from an outlet of said source of working fluid to said heat transfer element; and
a working fluid return path within said outer catheter body, from said heat transfer element to an inlet of said source of working fluid;
wherein said heat transfer element comprises a hollow tube in the form of a loop having two sides, each side of said loop comprising a coil.
Referenced Cited
U.S. Patent Documents
2308484 January 1943 Auzin et al.
2374609 April 1945 McCollum
2615686 October 1952 Davidson
2672032 March 1954 Towse
2913009 November 1959 Kuthe
3125096 March 1964 Antiles et al.
3298371 January 1967 Lee
3425419 February 1969 Dato
3504674 April 1970 Swenson et al.
3612175 October 1971 Ford et al.
3674031 July 1972 Weiche
3696813 October 1972 Wallach
3865116 February 1975 Brooks
3888259 June 1975 Miley
3971383 July 27, 1976 van Gerven
4038519 July 26, 1977 Foucras
4153048 May 8, 1979 Magrini
4190033 February 26, 1980 Foti
4231425 November 4, 1980 Engstrom
4275734 June 30, 1981 Mitchiner
4298006 November 3, 1981 Parks
4318722 March 9, 1982 Altman
4323071 April 6, 1982 Simpson et al.
4427009 January 24, 1984 Wells et al.
4445500 May 1, 1984 Osterholm
4483341 November 20, 1984 Witteles
4497890 February 5, 1985 Helbert
4502286 March 5, 1985 Okada et al.
4569355 February 11, 1986 Bitterly
4581017 April 8, 1986 Sahota
4602642 July 29, 1986 O'Hara et al.
4655746 April 7, 1987 Daniels et al.
4672962 June 16, 1987 Hershenson
4745922 May 24, 1988 Taylor
4748979 June 7, 1988 Hershenson
4750493 June 14, 1988 Brader
4762129 August 9, 1988 Bonzel
4762130 August 9, 1988 Fogarty et al.
4781799 November 1, 1988 Herbert, Jr. et al.
4820349 April 11, 1989 Saab
4860744 August 29, 1989 Johnson et al.
4883455 November 28, 1989 Leonard
4894164 January 16, 1990 Polaschegg
4904237 February 27, 1990 Janese
4920963 May 1, 1990 Brader
4951677 August 28, 1990 Crowley et al.
4964409 October 23, 1990 Tremulis
4973493 November 27, 1990 Guire
4979959 December 25, 1990 Guire
5000734 March 19, 1991 Boussignac et al.
5002531 March 26, 1991 Bonzel
5014695 May 14, 1991 Benak et al.
5018521 May 28, 1991 Campbell
5019075 May 28, 1991 Spears et al.
5024668 June 18, 1991 Peters et al.
5041089 August 20, 1991 Mueller et al.
5046497 September 10, 1991 Millar
5078713 January 7, 1992 Varney
5089260 February 18, 1992 Hunter et al.
5092841 March 3, 1992 Spears
5106360 April 21, 1992 Ishwara et al.
5108390 April 28, 1992 Potocky et al.
RE33911 May 5, 1992 Samson et al.
5110721 May 5, 1992 Anaise et al.
5112438 May 12, 1992 Bowers
5117822 June 2, 1992 Laghi
5147355 September 15, 1992 Friedman et al.
5149321 September 22, 1992 Klatz et al.
5150706 September 29, 1992 Cox et al.
5151100 September 29, 1992 Abele et al.
5180364 January 19, 1993 Ginsburg
5190539 March 2, 1993 Fletcher et al.
5191883 March 9, 1993 Lennox et al.
5196024 March 23, 1993 Barath
5211631 May 18, 1993 Sheaff
5234405 August 10, 1993 Klatz et al.
5241951 September 7, 1993 Mason et al.
5248312 September 28, 1993 Langberg
5250070 October 5, 1993 Parodi
5257977 November 2, 1993 Esbel
5264260 November 23, 1993 Saab
5267341 November 30, 1993 Shearin
5269369 December 14, 1993 Faghri
5269749 December 14, 1993 Koturov
5269758 December 14, 1993 Taheri
5281213 January 25, 1994 Milder et al.
5281215 January 25, 1994 Milder
5306261 April 26, 1994 Alliger et al.
5310440 May 10, 1994 Zingher
5322514 June 21, 1994 Steube et al.
5322515 June 21, 1994 Karas et al.
5322518 June 21, 1994 Schneider et al.
5330435 July 19, 1994 Vaillancourt
5330438 July 19, 1994 Gollobin et al.
5334193 August 2, 1994 Nardella
5340290 August 23, 1994 Clemens
5342181 August 30, 1994 Schock et al.
5342301 August 30, 1994 Saab
5344436 September 6, 1994 Fontenot et al.
5354186 October 11, 1994 Murtuza et al.
5365750 November 22, 1994 Greenthal
5368591 November 29, 1994 Lennox et al.
5383854 January 24, 1995 Safar et al.
5383918 January 24, 1995 Panetta
5395314 March 7, 1995 Klatz et al.
5395331 March 7, 1995 O'Neill et al.
5403281 April 4, 1995 O'Neill et al.
5417686 May 23, 1995 Peterson et al.
5423745 June 13, 1995 Todd et al.
5423807 June 13, 1995 Milder
5433740 July 18, 1995 Yamaguchi
5437673 August 1, 1995 Baust et al.
5443456 August 22, 1995 Alliger et al.
5462521 October 31, 1995 Brucker et al.
5486204 January 23, 1996 Clifton
5486208 January 23, 1996 Ginsburg
5496271 March 5, 1996 Burton et al.
5531776 July 2, 1996 Ward et al.
5549559 August 27, 1996 Eshel
5554119 September 10, 1996 Harrison et al.
5558644 September 24, 1996 Boyd et al.
5573532 November 12, 1996 Chang et al.
5578008 November 26, 1996 Hara
5584804 December 17, 1996 Klatz et al.
5588438 December 31, 1996 McKown et al.
5591162 January 7, 1997 Fletcher et al.
5620480 April 15, 1997 Rudie
5622182 April 22, 1997 Jaffe
5624392 April 29, 1997 Saab
5630837 May 20, 1997 Crowley
5643197 July 1, 1997 Brucker et al.
5647051 July 8, 1997 Neer
5653692 August 5, 1997 Masterson et al.
5709654 January 20, 1998 Klatz et al.
5713941 February 3, 1998 Robins et al.
5716386 February 10, 1998 Ward et al.
5733318 March 31, 1998 Augustine
5735809 April 7, 1998 Gorsuch
5787715 August 4, 1998 Dobak, III et al.
5797878 August 25, 1998 Bleam
5799661 September 1, 1998 Boyd et al.
5800480 September 1, 1998 Augustine et al.
5800483 September 1, 1998 Vought
5800516 September 1, 1998 Fine et al.
5807391 September 15, 1998 Wijkamp
5820593 October 13, 1998 Safar et al.
5824030 October 20, 1998 Yang et al.
5827222 October 27, 1998 Klatz et al.
5827237 October 27, 1998 Macoviak et al.
5827269 October 27, 1998 Saadat
5833671 November 10, 1998 Macoviak et al.
5837003 November 17, 1998 Ginsburg
5861021 January 19, 1999 Thome et al.
5868735 February 9, 1999 Lafontaine
5871526 February 16, 1999 Gibbs et al.
5873835 February 23, 1999 Hastings et al.
5879316 March 9, 1999 Safar et al.
5879329 March 9, 1999 Ginsburg
5899898 May 4, 1999 Arless et al.
5899899 May 4, 1999 Arless et al.
5901783 May 11, 1999 Dobak, III et al.
5902268 May 11, 1999 Saab
5906588 May 25, 1999 Safar et al.
5906594 May 25, 1999 Scarfone et al.
5906636 May 25, 1999 Casscells, III et al.
5913856 June 22, 1999 Chia et al.
5913885 June 22, 1999 Klatz et al.
5913886 June 22, 1999 Soloman
5916242 June 29, 1999 Schwartz
5957963 September 28, 1999 Dobak, III
5971979 October 26, 1999 Joye et al.
5989238 November 23, 1999 Ginsburg
6007692 December 28, 1999 Herbert et al.
6019783 February 1, 2000 Philips et al.
6022336 February 8, 2000 Zadno-Azizi et al.
6024740 February 15, 2000 Lesh et al.
6033383 March 7, 2000 Ginsburg
6042559 March 28, 2000 Dobak, III
6051019 April 18, 2000 Dobak, III
6096068 August 1, 2000 Dobak, III et al.
6110168 August 29, 2000 Ginsburg
6126684 October 3, 2000 Gobin et al.
6146411 November 14, 2000 Noda et al.
6146814 November 14, 2000 Millet
6149670 November 21, 2000 Worthen et al.
6149673 November 21, 2000 Ginsburg
6149676 November 21, 2000 Ginsburg
6149677 November 21, 2000 Dobak, III
6165207 December 26, 2000 Balding et al.
6235048 May 22, 2001 Dobak, III
6306161 October 23, 2001 Ginsburg
6315995 November 13, 2001 Pinsky et al.
6316403 November 13, 2001 Pinsky et al.
6354099 March 12, 2002 Bieberich
20010005791 June 28, 2001 Ginsburg et al.
20010016764 August 23, 2001 Dobak, III
20010047196 November 29, 2001 Ginsburg et al.
20010049545 December 6, 2001 Lasersohn et al.
20020029073 March 7, 2002 Schwartz
20020045852 April 18, 2002 Saab
Foreign Patent Documents
730835 January 1997 AU
739996 January 1999 AU
743945 February 2002 AU
0 655 225 May 1993 EP
0 664 990 November 1997 EP
2 447 406 March 1980 FR
806 029 February 1981 RU
WO 91/05528 May 1991 WO
WO 93/04727 March 1993 WO
WO 95/01814 January 1995 WO
WO 96/40347 December 1996 WO
WO 97/01374 January 1997 WO
WO 97/25011 July 1997 WO
WO 98/26831 June 1998 WO
WO 98/31312 July 1998 WO
WO 99/04211 January 1999 WO
WO 99/37226 July 1999 WO
WO 99/48449 September 1999 WO
WO 99/66970 December 1999 WO
WO 99/66971 December 1999 WO
WO 00/09054 February 2000 WO
WO 00/10494 March 2000 WO
WO 00/38601 July 2000 WO
WO 00/47145 August 2000 WO
WO 00/48670 August 2000 WO
WO 00/51534 September 2000 WO
WO 00/53135 September 2000 WO
WO 00/57823 October 2000 WO
WO 00/62837 October 2000 WO
WO 00/66053 November 2000 WO
WO 00/72779 December 2000 WO
WO 00/72787 December 2000 WO
WO 01/03606 January 2001 WO
WO 01/08580 February 2001 WO
WO 01/10323 February 2001 WO
WO 01/10365 February 2001 WO
WO 01/12061 February 2001 WO
WO 01/12122 February 2001 WO
WO 01/13809 March 2001 WO
WO 01/13837 March 2001 WO
WO 01/17471 March 2001 WO
WO 01/19447 March 2001 WO
WO 02/13710 February 2002 WO
WO 02/19934 March 2002 WO
Other references
  • Benzinger, T. H. “On Physical Heat Regulation and the Sensoe of Temperature in Man,” Proc. N.A.S. 45:645-650 (1959).
  • Cabanac, M. “Selective Brain Cooling and thermoregulatory Set-Point,” Journ. of Basic & Clinical Phsysiol. & Pharmacology 9 ( 1 ):3-13 (1998).
  • Cabanac, M. “Selective Brain Cooling in Humans: ‘Fancy’ or Fact?” Point-Counterpoint 7:1143-1147 (Sep. 1993).
  • Colvett, Kyle, A. F. Althausen, B. Bassil, N. M. Heney, F. V. McGovern, H. H. Young, D. S. Kaufman, A. L. Zietman, and W. U. Shipley, “Opportunities with Combined Modality Therapy for Selective Organ Preservation in Muscle-Invasive Bladder Cancer,” Journ. of Surg. Oncology 63:201-208 (1996).
  • Jessen, C., J. B. Mercer, and S. Puschmann “Intravascular Heat Exchanger for Conscious Goats,” Pflügers Arch. 268-265 (1977).
  • Maas, C., R. Kok, P. Segers, A. Boogaart, S. Eilander, I. de Vries, “Intermittent Antegrade/Selective Cerebral Perfusion During Circulatory Arrest for Repair of the Aortic Arch,” Perfusion 12:127-132 (1997).
  • Mercer, J. B. and C. Jessen, “Effects of Total Body Core Cooling on Heat Production of Conscious Goats,” Pflügers Arch. 373:259-267 (1978).
  • Schubert, A. “Side Effects of Mild Hypothermia,” Journ. of Neurosurgical Anesthesiology, 7 ( i2 ):139-147 (1995).
  • Ambrus; The Biphasic Nature and Temperature Dependence of the Activation of Human Plasminogen by Urokinase; May 1979; pp. 339-347; Research Communications in Chemical Pathology and Pharmacology, vol. 24, No. 2.
  • Bigelo; Hypothermia, Its Possible Role in Cardiac Surgery; Nov. 1959; pp. 849-866; Annals of Surgery, vol. 132, No. 5.
  • Cheatle; Cryostripping the Long and Short Saphenous Veins; Jan. 1993; p. 1283; Br. J. Surg., vol. 80.
  • Dexter; Blood Warms as It Blows Retrograde from a Femoral Cannulation Site to the Carotic Artery During Cardiopulmonary Bypass; Nov. 1994; pp. 393-397; Perfusion, vol. 9, No. 6.
  • Gillinov; Superior Cerebral Protection with Profound Hypothermia During Circulatory Arrest; Nov. 1992; pp. 1432-1439; Ann. Thorac. Surg., vol. 55.
  • Higazi; The Effect of Ultrasonic Irradiation and Temperature on Fibrinolytic Activity in Vitro; Aug. 1992; p. 251-253; Thrombosis Research, vol. 69, No. 2.
  • Imamaki; Retrograde Cerebral Perfusion with Hypothermic Blood Provides Efficient Protection of the Brain; Jul. 1995; pp. 325-333; Journal of Cardiac Surgery, vol. 10, No. 4, Part 1.
  • Jolin; Management of a Giant Intracranial Aneurysm Using Surface-Heparinized Extracorporeal Circulaiton and Controlled Deep Hypothermic Low Flow Perfusion; Aug. 1992; pp. 756-760; Acta Anaesthesiologica Scandinavia.
  • Jos R.C. Jansen, Ph.D., et al., Near Continuous Cardiac Output by Thermodilution, (1997), Journal of Clinical Monitoring 13:233-239.
  • Kimoto; Open Heart Surgery under Direct Vision with the Aid of Brain-Cooling by Irrigation; Jul. 1955; pp. 592-603; Surgery, vol. 39, No. 4.
  • Marekovic, Z; Abstract of Renal Ypothermia in Sistu by Venous Passages: Experimental Work on Dogs; 1980; Eur Urol 6(2); 1 page.
  • Meden; Effect of Hypothermia and Delayed Thrombolysis in a Rat Embolic Stroke Model; Dec. 1993; pp. 91-98; Acta Neurologica Scandinavica.
  • Meden; The Influence of Body Temperature on Infarct Volume and Thrombolytic Therapy in a Rat Embolic Stroke Model; Feb. 1994; pp. 131-138; Brain Research, vol. 647.
  • Milleret, Rene; La cryo-chirurgie danes les varices des mimbres inferieurs; Angiologie; Supplement au No. 110.
  • Milleret; Abstract of Cryosclerosis of the Saphenous Veins in Varicose Reflux in the Obese and Elderly; Oct. 1981; one page; Phlebologie, vol. 34, No. 4.
  • Parkins; Brain Cooling in the Prevention of Brain Damage During Periods of Circulatory Occlusion in Dogs; Apr. 1954; pp. 284-289; Annals of Surgery, vol. 140, No. 3.
  • Piepgras; Rapid Active Internal Core Cooling for Induction of Moderate Hypothermia in Head Injury by Use of an Extracorporeal Heat Exchanger; Feb. 1998; pp. 311-318; Neurosurgery, vol. 42, No. 2.
  • Rijken; Plasminogen Activation at Low Temperatures in Plasma Samples Containing Therapeutic Concentrations of Tissue-Type Plasminogen Activator or Other Thrombolytic Agents; Oct. 1989; pp. 47-52; place of publication unknown.
  • Schwartz, A.E. et al.; Isolated Cerebral Hypothermia by Single Carotid Artery Perfusion of Extracorporeally Cooled Blood in Baboons; (1996); Neurosurgery 39(3):577-582.
  • Schwartz; Cerebral Blood Flow During Low-flow Hypothermic Cardiopulmonary Bypass in Baboons; Jun. 1994; pp. 959-964; Anesthesiology, vol. 81, No. 4.
  • Schwartz, Selective Cerebral Hypothermia by Means of Transfemoral Internal Carotid Artery Catheterization; May 1996; pp. 571-572; Radiology, vol. 201, No. 2.
  • Steen; The Detrimental Effects of Prolonged Hypothermia and Rewarming in the Dog; Aug. 1979;pp. 224-230; Anesthesiology, vol. 52, No. 3.
  • Vandam; Hypothermia; Sep. 1959; pp. 546-553; The New England Journal of Medicine.
  • White; Cerebral Hypothermia and Circulatory Arrest; Jul. 1978; pp. 450-458; Mayo Clinic Proceedings, vol. 53.
  • Yenari; Thrombolysis with Tissue Plasminogen Activator ( tPA ) is temerature Dependent; Jul. 1994; pp. 475-481; Thrombosis Research, vol. 77, No. 5.
  • Yoshihara; Changes in Coagulation and Fibrinolysis Occurring in Dogs during Hypothermia; Aug. 1984; pp. 503-512; Thrombosis Research, vol. 37, No. 4.
  • Zarins; Circulation in Profound Hypothermia; Nov. 1972; pp. 97-104; Journal of Surgical Research, vol. 14, N. 2.
Patent History
Patent number: 6482226
Type: Grant
Filed: Aug 30, 2000
Date of Patent: Nov 19, 2002
Assignee: Innercool Therapies, Inc. (San Diego, CA)
Inventor: John D. Dobak, III (Jolla, CA)
Primary Examiner: Roy D. Gibson
Attorney, Agent or Law Firm: Gerald W. Spinks
Application Number: 09/650,940
Classifications
Current U.S. Class: With Fluid Supply (607/104); Blood (607/106); Cyrogenic Application (606/20)
International Classification: A61F/700;